A Six-year Follow-up Study on the Prognosis in Elderly Patients with Ischemic Stroke Combined with Atrial Fibrillation and Coronary Heart Disease

doi:10.12114/j.issn.1007-9572.2021.00.527

Abstract

Abstract: Background　In recent years，patients with atrial fibrillation and coronary heart disease have attracted more and more attention in clinic.Recent clinical studies mainly focused on the prevention and treatment of stroke and thromboembolic events.Objective　To evaluate the long-term survival rate of elderly patients with ischemic stroke combined with atrial fibrillation and coronary heart disease，and analyze the risk factors which affected the prognosis.Methods　We conducted a retrospective cohort study.A retrospective analysis of 406 patients over 60 years admitted to hospital due to acute ischemic stroke for the first time were enrolled，and 164 patients with atrial fibrillation and coronary heart disease were selected from them as cerebrovascular disease group，164 patients without cerebrovascular disease but with atrial fibrillation and coronary heart disease matched with age，gender and comorbidities were selected from concurrent hospitalized patients in the Department of Cardiology as non-cerebrovascular disease group.The clinical data，including demographic information，types of diseases，types of medications，blood pressure，heart rate，cardiovascular diseases and other diseases of the two groups were collected，laboratory test，echocardiographic parameters，treatment plan.The CHA2DS2-VASc score and CHADS2 score were used to assess the risk of stroke and thromboembolism，and the HAS-BLED score was used to assess the risk of bleeding.The patients were followed up for at least 6 years by telephone，outpatient and inpatient records after discharge，to record the death，readmission and major adverse cardiovascular events（MACE），and to explore the factors that affect his long-term prognosis.Results　Compared with non-cerebrovascular disease group，the proportion of hyperlipidemia and chronic gastrointestinal disease in cerebrovascular disease group was lower.LVEDD，CHA2DS2-VASc score，CHADS2 score，and the HAS-BLED score in cerebrovascular disease group were higher（P<0.05）.In the 164 patients with cerebrovascular disease group，2 cases were lost to follow-up（1.2%），and 80 cases died（49.4%）.They were divided into death group（80 cases） and survival group（82 cases） according to the survival outcome.The death group was older and had lower systolic and diastolic blood pressure than the survival group，and the proportion of hypertension，hyperlipidemia，serum albumin and the use of statins were also lower than the survival group.The resting heart rate and the proportion of old myocardial infarction，the proportion of heart failure，chronic kidney disease，NYHA，D-dimer and NT-proBNP levels in death group were higher than the survival group（P<0.05）.The results of multivariate Cox regression analysis showed that for every 10 years of age increase〔HR=1.63，95%CI（1.05，2.51）〕，history of old myocardial infarction〔HR=2.19，95%CI（1.14，4.22）〕 and D-Dimer ≥148 μg/L〔HR=6.99，95%CI（2.10，23.28）〕 were independent risk factors for long-term mortality in elderly patients with ischemic stroke combined with atrial fibrillation and coronary heart disease，while hypertension〔HR=0.28，95%CI（0.11，0.72）〕 and statins use〔HR=0.38，95%CI（0.19，0.78）〕 were the protective factors for long-term death in these patients.Conclusion　The long-term mortality of patients with atrial fibrillation and coronary heart disease after the first occurrence of cerebrovascular disease is not related to the coexisting cerebrovascular disease，but related to aging，history of old myocardial infarction and D-dimer level.Maintaining an appropriate blood pressure level and using statins may reduce the long-term mortality patients with atrial fibrillation and coronary heart disease.

Key words: Brain ischemia, Stroke, Atrial fibrillation, Coronary disease, Aged, Death, Major adverse cardiovascular events, Follow-up studies

摘要： 背景　近年来，心房颤动（简称房颤）合并冠心病患者在临床上越来越受到关注，新近的临床研究主要集中于脑卒中和血栓栓塞事件的预防和治疗。目的　评估老年缺血性脑卒中合并房颤及冠心病患者的远期生存率，分析影响预后的危险因素。方法　本研究为回顾性队列研究，回顾性分析2012年1月—2014年10月首次因急性缺血性脑卒中入住北京医院神经内科病房的患者406例，从中选取同时满足房颤和冠心病诊断标准的60岁以上老年患者共计164例作为脑血管病组，并从心内科同期住院患者中选取年龄、性别、共病种类与其相匹配的房颤合并冠心病但无脑血管病患者164例作为非脑血管病组。收集两组患者的临床资料：包含人口统计学信息、疾病种类、用药种类、血压、心率、合并心脏基础疾病及其他疾病、实验室指标、超声心动图结果、治疗方案；分别通过CHA2DS2-VASc评分、CHADS2评分评估患者的脑卒中及血栓栓塞发生风险，应用HAS-BLED评分评估出血风险，并在其出院后通过定期电话随访、门诊及住院志查询等方式随访至少6年，记录其死亡、再住院次数及主要不良心血管事件（MACE）发生情况，探讨影响其远期预后的因素。结果　脑血管病组合并高脂血症比例、慢性胃肠病比例低于非脑血管病组，LVEDD、CHA2DS2-VASc评分、CHADS2评分、HAS-BLED评分高于非脑血管病组（P<0.05）。脑血管病组164例患者失访2例（失访率1.2%），死亡80例（49.4%），根据生存结局分为死亡组（80例）和存活组（82例）。死亡组患者年龄大于存活组，收缩压、舒张压、合并高血压比例、合并高脂血症比例、血清蛋白、使用他汀类药物比例低于存活组，心率和合并陈旧性心肌梗死、心力衰竭、慢性肾病比例及纽约心脏病协会（NYHA）心功能分级、D-二聚体、N末端B型钠尿肽前体（NT-proBNP）高于存活组（P<0.05）。多因素Cox比例风险回归模型分析结果显示，年龄每增加10岁〔HR=1.63，95%CI（1.05，2.51）〕、陈旧性心肌梗死〔HR=2.19，95%CI（1.14，4.22）〕和D-二聚体≥148 μg/L〔HR=6.99，95%CI（2.10，23.28）〕是老年缺血性脑卒中合并房颤及冠心病患者远期死亡的危险因素，高血压〔HR=0.28，95%CI（0.11，0.72）〕和使用他汀类药物〔HR=0.38，95%CI（0.19，0.78）〕是患者远期死亡的保护因素。结论　房颤合并冠心病患者在首次发生脑血管病后，其远期死亡与并存的脑血管病无关，而与增龄、陈旧性心肌梗死病史及D-二聚体水平有关，维持适当高的血压水平和应用他汀类药物可能会降低远期死亡率。

关键词: 脑缺血, 卒中, 心房颤动, 冠心病, 老年人, 死亡, 主要不良心血管事件, 随访研究

DONG Min,XU Lei,HE Qinghua, et al. A Six-year Follow-up Study on the Prognosis in Elderly Patients with Ischemic Stroke Combined with Atrial Fibrillation and Coronary Heart Disease　[J]. Chinese General Practice, 2021, 24(17): 2148-2156. DOI: 10.12114/j.issn.1007-9572.2021.00.527.
董敏,徐蕾,何清华等. 老年缺血性脑卒中合并心房颤动及冠心病患者的6年预后随访研究[J]. 中国全科医学, 2021, 24(17): 2148-2156. DOI: 10.12114/j.issn.1007-9572.2021.00.527.

References

［1］FEIGIN V L，KRISHNAMURTHI R V，PARMAR P，et al．Update on the global burden of ischemic and hemorrhagic stroke in 1990-2013：the GBD 2013 study［J］．Neuroepidemiology，2015，45（3）：161-176．DOI：10.1159/000441085.
［2］ARBOIX A，CARTANYÀ A，LOWAK M，et al．Gender differences and woman-specific trends in acute stroke：results from a hospital-based registry （1986—2009）［J］．Clin Neurol Neurosurg，2014，127：19-24．DOI：10.1016/j.clineuro.2014.09.024.
［3］中华医学会神经病学分会，中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2018［J］．中华神经科杂志，2018，51（9）：666-682．DOI：10.3760/cma.j.issn.1006-7876.2018.09.004.
Chinese Society of Neurology，Chinese Stroke Society.Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018［J］．Chin J Neurol，2018，51（9）：666-682．DOI：10.3760/cma.j.issn.1006-7876.2018.09.004.
［4］FEIGIN V L，KRISHNAMURTHI R V，BARKER-COLLO S，et al．
30-year trends in stroke rates and outcome in Auckland，new Zealand （1981—2012）：a multi-ethnic population-based series of studies［J］．PLoS One，2015，10（8）：e0134609．DOI：10.1371/journal.pone.0134609.
［5］YAMANOUCHI H.Cerebral embolism in elderly patients with atrial fibrillation［J］．Nihon Ronen Igakkai Zasshi，1993，30（5）：348-353．DOI：10.3143/geriatrics.30.348.
［6］ GLADER E L，SJÖLANDER M，ERIKSSON M，et al．Persistent use of secondary preventive drugs declines rapidly during the first 2 years after stroke［J］．Stroke，2010，41（2）：397-401．DOI：10.1161/STROKEAHA.109.566950.
［7］中华医学会神经病学分会，中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2014［J］．中华神经科杂志，2015，48（4）：246-257．DOI：10.3760/cma.j.issn.1006-7876.2015.04.002.
［8］JANUARY C T，WANN L S，CALKINS H，et al．2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation：a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration with the Society of Thoracic Surgeons［J］．Circulation，2019，140（2）：e125-151．DOI：10.1161/CIR.0000000000000665.
［9］JANUARY C T，WANN L S，ALPERT J S，et al．2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation：a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society［J］．J Am Coll Cardiol，2014，64（21）：e1-76．DOI：10.1016/j.jacc.2014.03.022.
［10］SCHWANDT A，DENKINGER M，FASCHING P，et al．Comparison of MDRD，CKD-EPI，and Cockcroft-Gault equation in relation to measured glomerular filtration rate among a large cohort with diabetes［J］．J Diabetes Complications，2017，31（9）：1376-1383．DOI：10.1016/j.jdiacomp.2017.06.016.
［11］RADISAUSKAS R，TAMOSIUNAS A，KRANCIUKAITE-BUTYLKINIENE D，et al．Long-term survival after stroke in Lithuania：Data from Kaunas population-based stroke registry［J］．PLoS One，2019，14（7）：e0219392．DOI：10.1371/journal.pone.0219392.
［12］KULESH S D，KASTSINEVICH T M，KLIATSKOVA L A，et al．
Long-term outcome after stroke in Belarus：the Grodno stroke study［J］．Stroke，2011，42（11）：3274-3276．DOI：10.1161/STROKEAHA.111.625400.
［13］KHANEVSKI A N，BJERKREIM A T，NOVOTNY V，et al．Recurrent ischemic stroke：incidence，predictors，and impact on mortality［J］．Acta Neurol Scand，2019，140（1）：3-8．DOI：10.1111/ane.13093.
［14］ALBERTS M，CHEN Y W，LIN J H，et al．Risks of stroke and mortality in atrial fibrillation patients treated with rivaroxaban and warfarin［J］．Stroke，2020，51（2）：549-555．DOI：10.1161/STROKEAHA.119.025554.
［15］AVAN A，DIGALEH H，DI NAPOLI M，et al．Socioeconomic status and stroke incidence，prevalence，mortality，and worldwide burden：an ecological analysis from the Global Burden of Disease Study 2017［J］．BMC Med，2019，17（1）：191．DOI：10.1186/s12916-019-1397-3.
［16］MAN S M，XIAN Y，HOLMES D N，et al．Association between thrombolytic door-to-needle time and 1-year mortality and readmission in patients with acute ischemic stroke［J］．JAMA，2020，323（21）：2170-2184．DOI：10.1001/jama.2020.5697.
［17］LI S，PENG Y，WANG X，et al．Cardiovascular events and death after myocardial infarction or ischemic stroke in an older Medicare population［J］．Clin Cardiol，2019，42（3）：391-399．DOI：10.1002/clc.23160.
［18］HINDRICKS G，POTPARA T，DAGRES N，et al．2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery （EACTS）［J］．Eur Heart J，2021，42（5）：373-498．DOI：10.1093/eurheartj/ehaa612.
［19］杨玉辉，郑卫星，黄明方，等．单中心非瓣膜病心房颤动患者抗凝治疗状况分析［J］．中国医刊，2019，54（1）：27-30．DOI：10.3969/j.issn.1008-1070.2019.01.007.
YANG Y H，ZHENG W X，HUANG M F，et al．A single center analysis of anticoagulant therapy in patients with nonvalvular atrial fibrillation［J］．Chin J Med，2019，54（1）：27-30．DOI：10.3969/j.issn.1008-1070.2019.01.007.
［20］孙艺红，胡大一．非瓣膜性心房颤动患者全球抗凝注册研究中国亚组基线数据分析［J］．中华心血管病杂志，2014，42（10）：846-850．DOI：10.3760/cma.j.issn.0253-3758.2014.10.011.
［21］WOLF P A，ABBOTT R D，KANNEL W B.Atrial fibrillation as an independent risk factor for stroke：the Framingham Study［J］．Stroke，1991，22（8）：983-988．DOI：10.1161/01.str.22.8.983.
［22］AMBALE-VENKATESH B，YANG X Y，WU C O，et al．Cardiovascular event prediction by machine learning：the multi-ethnic study of atherosclerosis［J］．Circ Res，2017，121（9）：1092-1101．DOI：10.1161/CIRCRESAHA.117.311312.
［23］KADESJÖ E，ROOS A，SIDDIQUI A J，et al．Causes of death in patients with acute and chronic myocardial injury［J］．Am J Med，2020，133（5）：590-598.e2．DOI：10.1016/j.amjmed.2019.09.030.
［24］PAN Y，QIU Q，REN WH，et al．Long-term outcomes of implanting drug-eluting stents for unprotected left main coronary artery disease patients with left ventricular systolic dysfunction［J］．Zhonghua Yi Xue Za Zhi，2017，97（46）：3612-3616．DOI：10.3760/cma.j.issn.0376-2491.2017.46.003.
［25］GAZOVÁ A，LEDDY J J，REXOVÁ M，et al．Predictive value of CHA2DS2-VASc scores regarding the risk of stroke and all-cause mortality in patients with atrial fibrillation （CONSORT compliant）［J］．Medicine （Baltimore），2019，98（31）：e16560．DOI：10.1097/MD.0000000000016560.
［26］ZHOU X B，CAO K W，KOU S Q，et al．Usefulness of CHADS2 score for prognostic stratification of patients with coronary artery disease：a systematic review and meta-analysis of cohort studies［J］．Int J Cardiol，2017，228：906-911．DOI：10.1016/j.ijcard.2016.11.114.
［27］ORVIN K，BENTAL T，ASSALI A，et al．Usefulness of the CHA2DS2-VASC score to predict adverse outcomes in patients having percutaneous coronary intervention［J］．Am J Cardiol，2016，117（9）：1433-1438．DOI：10.1016/j.amjcard.2016.02.010.
［28］KONISHI H，MIYAUCHI K，TSUBOI S，et al．Impact of the HAS-BLED score on long-term outcomes after percutaneous coronary intervention［J］．Am J Cardiol，2015，116（4）：527-531．DOI：10.1016/j.amjcard.2015.05.015.
［29］KWON C H，KANG J G，LEE H J，et al．C-reactive protein and risk of atrial fibrillation in East Asians［J］．Europace，2017，19（10）：1643-1649．DOI：10.1093/europace/euw298.
［30］KIM T W，SONG I U，CHUNG S W，et al．Serum D-dimer levels are proportionally associated with left atrial enlargement in patients with an acute ischemic stroke due to non-valvular atrial fibrillation［J］．Intern Med，2016，55（11）：1447-1452．DOI：10.2169/internalmedicine.55.6087.
［31］杨蕾，高可，付博文，等．血液生物标志物联合CHA2DS2-VASc评分对非瓣膜性心房颤动患者发生急性脑梗死的预测价值［J］．中国医刊，2020，55（1）：31-35．DOI：10.3969/j.issn.1008-1070.2020.01.009.
YANG L，GAO K，FU B W，et al．Predictive value of blood biomarkers combined with CHA2DS2-VASc score for acute cerebral embolism in patients with non-valvular atrial fibrillation［J］．Chin J Med，2020，55（1）：31-35．DOI：10.3969/j.issn.1008-1070.2020.01.009.
［32］NARUSE H，ISHII J，TAKAHASHI H，et al．Prognostic value of combination of plasma D-dimer concentration and estimated glomerular filtration rate in predicting long-term mortality of patients with stable coronary artery disease［J］．Circ J，2017，81（10）：1506-1513．DOI：10.1253/circj.CJ-16-1272.
［33］徐常清，陈夏玲，张东生，等．急性缺血性脑卒中机械取栓患者围手术期血压水平对预后的影响［J］．医学理论与实践，2021，34（1）：41-43．DOI：10.19381/j.issn.1001-7585.2021.01.015.
［34］FURLAN N E，SOUZA J T，BAZAN S G Z，et al．Association between statin use and mortality risks during the acute phase of ischemic stroke in patients admitted to an intensive care unit［J］．Arq Neuropsiquiatr，2020，78（3）：158-162．DOI：10.1590/0004-282x20190172.
［35］YUM K S，CHANG J Y，JEONG W J，et al．Effect of statin on progression of symptomatic basilar artery Stenosis and subsequent ischemic stroke［J］．PLoS One，2017，12（10）：e0183798．DOI：10.1371/journal.pone.0183798.
［36］CHOI K H，SEO W K，PARK M S，et al．Effect of statin therapy on outcomes of patients with acute ischemic stroke and atrial fibrillation［J］．J Am Heart Assoc，2019，8（24）：e013941．DOI：10.1161/JAHA.119.013941.
［37］LEE M J，BANG O Y，KIM S J，et al．Role of statin in atrial fibrillation-related stroke：an angiographic study for collateral flow［J］．Cerebrovasc Dis，2014，37（2）：77-84．DOI：10.1159/000356114.
［38］HERTTUA K，MARTIKAINEN P，BATTY G D，et al．Poor adherence to statin and antihypertensive therapies as risk factors for fatal stroke［J］．J Am Coll Cardiol，2016，67（13）：1507-1515．DOI：10.1016/j.jacc.2016.01.044.
［39］RIST P M，BURING J E，RIDKER P M，et al．Lipid levels and the risk of hemorrhagic stroke among women［J］．Neurology，2019，92（19）：e2286-2294．DOI：10.1212/wnl.0000000000007454.

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